Erschienen in:
01.06.2013 | Original Paper
KCNN4 Channels participate in the EMT induced by PRL-3 in colorectal cancer
verfasst von:
Wei Lai, Lu Liu, Yujie Zeng, Heng Wu, Heyang Xu, Shuang Chen, Zhonghua Chu
Erschienen in:
Medical Oncology
|
Ausgabe 2/2013
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Abstract
Studies have shown that phosphatase of regenerating liver-3 (PRL-3) promotes the invasion, migration, and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition (EMT). However, the mechanism by which PRL-3 induces tumor cell EMT is unknown. Our previous research revealed that PRL-3 promotes LoVo cell proliferation by up-regulating KCNN4 channels. In the current study, we explored the mechanism by which PRL-3 mediates EMT. We demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. Further studies revealed that KCNN4 channels increased intracellular calcium levels and activated components of cell signaling downstream of calcium, including CaM-kinase II and glycogen synthase kinase-3 beta (GSK-3 beta), which increased Snail expression. Inhibiting KCNN4 with siRNA and TRAM-34, a specific inhibitor, restored E-cadherin expression and inhibited Snail expression. These results implicated the up-regulation of KCNN4 channels in the PRL-3-mediated induction of EMT and promotion of cancer metastasis.